JP2015527401A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2015527401A5 JP2015527401A5 JP2015531259A JP2015531259A JP2015527401A5 JP 2015527401 A5 JP2015527401 A5 JP 2015527401A5 JP 2015531259 A JP2015531259 A JP 2015531259A JP 2015531259 A JP2015531259 A JP 2015531259A JP 2015527401 A5 JP2015527401 A5 JP 2015527401A5
- Authority
- JP
- Japan
- Prior art keywords
- amino
- pyrazolo
- fluoro
- pyrimidin
- enenitrile
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 Oxetane-3-yl Chemical group 0.000 claims 54
- 150000001875 compounds Chemical class 0.000 claims 48
- 239000008194 pharmaceutical composition Substances 0.000 claims 31
- 150000003839 salts Chemical class 0.000 claims 29
- 239000011780 sodium chloride Substances 0.000 claims 29
- 239000000203 mixture Substances 0.000 claims 23
- 125000000217 alkyl group Chemical group 0.000 claims 19
- 229910052739 hydrogen Inorganic materials 0.000 claims 12
- 239000001257 hydrogen Substances 0.000 claims 12
- 150000002431 hydrogen Chemical class 0.000 claims 10
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 8
- 125000001188 haloalkyl group Chemical group 0.000 claims 8
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims 8
- NNGVMERLTTVLQP-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enenitrile Chemical compound C1CN(C)CCN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 NNGVMERLTTVLQP-DEOSSOPVSA-N 0.000 claims 7
- LCFFREMLXLZNHE-RUZDIDTESA-N CC(C)(C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCN(CC1)C1COC1 Chemical compound CC(C)(C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCN(CC1)C1COC1 LCFFREMLXLZNHE-RUZDIDTESA-N 0.000 claims 7
- 201000010099 disease Diseases 0.000 claims 7
- 206010040767 Sjogren's syndrome Diseases 0.000 claims 6
- 125000001475 halogen functional group Chemical group 0.000 claims 6
- 125000004193 piperazinyl group Chemical group 0.000 claims 6
- NNGVMERLTTVLQP-XMMPIXPASA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enenitrile Chemical compound C1CN(C)CCN1C(C)(C)C=C(C#N)C(=O)N1C[C@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 NNGVMERLTTVLQP-XMMPIXPASA-N 0.000 claims 5
- LCFFREMLXLZNHE-VWLOTQADSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CCN(CC2)C2COC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 LCFFREMLXLZNHE-VWLOTQADSA-N 0.000 claims 4
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 4
- 206010013774 Dry eye Diseases 0.000 claims 4
- 208000000429 Leukemia, Lymphocytic, Chronic, B-Cell Diseases 0.000 claims 4
- 125000002252 acyl group Chemical group 0.000 claims 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 4
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 4
- MWAPCVRIQHXPBI-UHFFFAOYSA-N CC(C=CC#N)(C)N1CCN(CC1)C1COC1 Chemical compound CC(C=CC#N)(C)N1CCN(CC1)C1COC1 MWAPCVRIQHXPBI-UHFFFAOYSA-N 0.000 claims 3
- 125000003545 alkoxy group Chemical group 0.000 claims 3
- 229910052757 nitrogen Inorganic materials 0.000 claims 3
- 208000009094 Anemia, Hemolytic, Autoimmune Diseases 0.000 claims 2
- 208000006673 Asthma Diseases 0.000 claims 2
- 206010003816 Autoimmune disease Diseases 0.000 claims 2
- 208000009899 Burkitt Lymphoma Diseases 0.000 claims 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims 2
- 206010012818 Diffuse large B-cell lymphoma Diseases 0.000 claims 2
- 206010018651 Graft versus host disease Diseases 0.000 claims 2
- 208000009329 Graft vs Host Disease Diseases 0.000 claims 2
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 claims 2
- 206010025135 Lupus erythematosus Diseases 0.000 claims 2
- 208000006557 Lymphoma, B-Cell, Marginal Zone Diseases 0.000 claims 2
- 206010025323 Lymphomas Diseases 0.000 claims 2
- 206010028417 Myasthenia gravis Diseases 0.000 claims 2
- 206010025310 Other lymphomas Diseases 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
- 206010046851 Uveitis Diseases 0.000 claims 2
- 206010047115 Vasculitis Diseases 0.000 claims 2
- 201000008937 atopic dermatitis Diseases 0.000 claims 2
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims 2
- 201000011510 cancer Diseases 0.000 claims 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 200000000018 inflammatory disease Diseases 0.000 claims 2
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 claims 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
- 201000009251 multiple myeloma Diseases 0.000 claims 2
- 239000000546 pharmaceutic aid Substances 0.000 claims 2
- 201000004681 psoriasis Diseases 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- YDXOXEUWKYKVDD-XMMPIXPASA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-[cyclopropyl(oxetan-3-yl)amino]-4-methylpent-2-enenitrile Chemical compound C([C@H]1CCCN1C(=O)C(C#N)=CC(C)(C)N(C1CC1)C1COC1)N(C1=NC=NC(N)=C11)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 YDXOXEUWKYKVDD-XMMPIXPASA-N 0.000 claims 1
- BYINIOQJRGRANK-HSZRJFAPSA-N 2-[(2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carbonyl]-4-[ethyl(oxetan-3-yl)amino]-4-methylpent-2-enenitrile Chemical compound N1([C@H](CCC1)CN1C2=NC=NC(N)=C2C(C=2C(=CC(OC=3C=CC=CC=3)=CC=2)F)=N1)C(=O)C(C#N)=CC(C)(C)N(CC)C1COC1 BYINIOQJRGRANK-HSZRJFAPSA-N 0.000 claims 1
- JYZBKNSSHGQRHT-XMMPIXPASA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethyl-5-morpholin-4-ylpent-2-enenitrile Chemical compound C([C@@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC(C)(C)CN1CCOCC1 JYZBKNSSHGQRHT-XMMPIXPASA-N 0.000 claims 1
- QMASBPPNEAZIMQ-AREMUKBSSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(4-tert-butylpiperazin-1-yl)-4-methylpent-2-enenitrile Chemical compound C1CN(C(C)(C)C)CCN1C(C)(C)C=C(C#N)C(=O)N1C[C@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 QMASBPPNEAZIMQ-AREMUKBSSA-N 0.000 claims 1
- UOQXGGUYVNGNOP-XMMPIXPASA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(6,8-dihydro-5H-imidazo[1,2-a]pyrazin-7-yl)-4-methylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CC3=NC=CN3CC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 UOQXGGUYVNGNOP-XMMPIXPASA-N 0.000 claims 1
- HFIXFIUHIPEHNT-JBRSBNLGSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-4-methylpent-2-enenitrile Chemical compound C[C@@H]1CN[C@@H](C)CN1C(C)(C)C=C(C#N)C(=O)N1C[C@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 HFIXFIUHIPEHNT-JBRSBNLGSA-N 0.000 claims 1
- HFIXFIUHIPEHNT-GIFXNVAJSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-[(2S,5R)-2,5-dimethylpiperazin-1-yl]-4-methylpent-2-enenitrile Chemical compound C[C@H]1CN[C@H](C)CN1C(C)(C)C=C(C#N)C(=O)N1C[C@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 HFIXFIUHIPEHNT-GIFXNVAJSA-N 0.000 claims 1
- KUEKVNDHYGCERM-XMMPIXPASA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-[cyclopropyl(oxetan-3-yl)amino]-4-methylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N(C2CC2)C2COC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KUEKVNDHYGCERM-XMMPIXPASA-N 0.000 claims 1
- UICSJEUOZPPJED-BFLUCZKCSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[(2R,5S)-2,4,5-trimethylpiperazin-1-yl]pent-2-enenitrile Chemical compound C[C@@H]1CN(C)[C@@H](C)CN1C(C)(C)C=C(C#N)C(=O)N1C[C@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 UICSJEUOZPPJED-BFLUCZKCSA-N 0.000 claims 1
- UICSJEUOZPPJED-RMTZWNOUSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[(2S,5R)-2,4,5-trimethylpiperazin-1-yl]pent-2-enenitrile Chemical compound C[C@H]1CN(C)[C@H](C)CN1C(C)(C)C=C(C#N)C(=O)N1C[C@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 UICSJEUOZPPJED-RMTZWNOUSA-N 0.000 claims 1
- HGXITWGZZVLXPJ-HSZRJFAPSA-N 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-piperazin-1-ylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CCNCC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 HGXITWGZZVLXPJ-HSZRJFAPSA-N 0.000 claims 1
- JYZBKNSSHGQRHT-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethyl-5-morpholin-4-ylpent-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC(C)(C)CN1CCOCC1 JYZBKNSSHGQRHT-DEOSSOPVSA-N 0.000 claims 1
- CMCZKFPSGLRSEQ-VWLOTQADSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(4-ethylpiperazin-1-yl)-4-methylpent-2-enenitrile Chemical compound C1CN(CC)CCN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 CMCZKFPSGLRSEQ-VWLOTQADSA-N 0.000 claims 1
- QMASBPPNEAZIMQ-SANMLTNESA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(4-tert-butylpiperazin-1-yl)-4-methylpent-2-enenitrile Chemical compound C1CN(C(C)(C)C)CCN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 QMASBPPNEAZIMQ-SANMLTNESA-N 0.000 claims 1
- UOQXGGUYVNGNOP-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-(6,8-dihydro-5H-imidazo[1,2-a]pyrazin-7-yl)-4-methylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CC3=NC=CN3CC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 UOQXGGUYVNGNOP-DEOSSOPVSA-N 0.000 claims 1
- HFIXFIUHIPEHNT-ARNLJNQMSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-4-methylpent-2-enenitrile Chemical compound C[C@@H]1CN[C@@H](C)CN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 HFIXFIUHIPEHNT-ARNLJNQMSA-N 0.000 claims 1
- HFIXFIUHIPEHNT-CUYJMHBOSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-[(2S,5R)-2,5-dimethylpiperazin-1-yl]-4-methylpent-2-enenitrile Chemical compound C[C@H]1CN[C@H](C)CN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 HFIXFIUHIPEHNT-CUYJMHBOSA-N 0.000 claims 1
- DEUQAIWVYRNFIH-ARNLJNQMSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-[(3S,5R)-3,5-dimethylpiperazin-1-yl]-4-methylpent-2-enenitrile Chemical compound C1[C@@H](C)N[C@@H](C)CN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 DEUQAIWVYRNFIH-ARNLJNQMSA-N 0.000 claims 1
- NIYAGZIDNIWGFF-SANMLTNESA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-[4-(2-methoxyethyl)piperazin-1-yl]-4-methylpent-2-enenitrile Chemical compound C1CN(CCOC)CCN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 NIYAGZIDNIWGFF-SANMLTNESA-N 0.000 claims 1
- KUEKVNDHYGCERM-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-[cyclopropyl(oxetan-3-yl)amino]-4-methylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N(C2CC2)C2COC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KUEKVNDHYGCERM-DEOSSOPVSA-N 0.000 claims 1
- FMEWHTMZZYPJGN-QHCPKHFHSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-[ethyl(oxetan-3-yl)amino]-4-methylpent-2-enenitrile Chemical compound C([C@H](CCC1)N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)N1C(=O)C(C#N)=CC(C)(C)N(CC)C1COC1 FMEWHTMZZYPJGN-QHCPKHFHSA-N 0.000 claims 1
- XTBYTIMEUSLGIH-QHCPKHFHSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)pent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CC3(COC3)C2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 XTBYTIMEUSLGIH-QHCPKHFHSA-N 0.000 claims 1
- SGXVGVKVFFHVGS-QHCPKHFHSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(4-methyl-3-oxopiperazin-1-yl)pent-2-enenitrile Chemical compound C1C(=O)N(C)CCN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 SGXVGVKVFFHVGS-QHCPKHFHSA-N 0.000 claims 1
- UICSJEUOZPPJED-GSLIJJQTSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[(2R,5S)-2,4,5-trimethylpiperazin-1-yl]pent-2-enenitrile Chemical compound C[C@@H]1CN(C)[C@@H](C)CN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 UICSJEUOZPPJED-GSLIJJQTSA-N 0.000 claims 1
- UICSJEUOZPPJED-USZFVNFHSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[(2S,5R)-2,4,5-trimethylpiperazin-1-yl]pent-2-enenitrile Chemical compound C[C@H]1CN(C)[C@H](C)CN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 UICSJEUOZPPJED-USZFVNFHSA-N 0.000 claims 1
- ZKIWYNDTGRBYQF-GSLIJJQTSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[(3S,5R)-3,4,5-trimethylpiperazin-1-yl]pent-2-enenitrile Chemical compound C1[C@@H](C)N(C)[C@@H](C)CN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 ZKIWYNDTGRBYQF-GSLIJJQTSA-N 0.000 claims 1
- NOXVOMASUWKHPG-DEOSSOPVSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(2,2,2-trifluoroethyl)piperazin-1-yl]pent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CCN(CC(F)(F)F)CC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 NOXVOMASUWKHPG-DEOSSOPVSA-N 0.000 claims 1
- HGXITWGZZVLXPJ-QHCPKHFHSA-N 2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-piperazin-1-ylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2CCNCC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 HGXITWGZZVLXPJ-QHCPKHFHSA-N 0.000 claims 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
- KDEQUORYXKLAFZ-UHFFFAOYSA-N 3-(2-fluoro-4-phenoxyphenyl)-2H-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C=12C(N)=NC=NC2=NNC=1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KDEQUORYXKLAFZ-UHFFFAOYSA-N 0.000 claims 1
- YLPIYCASFDJXFO-VWLOTQADSA-N 4-(4-acetylpiperazin-1-yl)-2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C1CN(C(=O)C)CCN1C(C)(C)C=C(C#N)C(=O)N1C[C@@H](N2C3=NC=NC(N)=C3C(C=3C(=CC(OC=4C=CC=CC=4)=CC=3)F)=N2)CCC1 YLPIYCASFDJXFO-VWLOTQADSA-N 0.000 claims 1
- KVLHSLKAKZYMEZ-CLJLJLNGSA-N 4-[(9aR)-3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl]-2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2C[C@@H]3COCCN3CC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KVLHSLKAKZYMEZ-CLJLJLNGSA-N 0.000 claims 1
- KVLHSLKAKZYMEZ-IZZNHLLZSA-N 4-[(9aR)-3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl]-2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2C[C@@H]3COCCN3CC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KVLHSLKAKZYMEZ-IZZNHLLZSA-N 0.000 claims 1
- KVLHSLKAKZYMEZ-FTJBHMTQSA-N 4-[(9aS)-3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl]-2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2C[C@H]3COCCN3CC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KVLHSLKAKZYMEZ-FTJBHMTQSA-N 0.000 claims 1
- KVLHSLKAKZYMEZ-UIOOFZCWSA-N 4-[(9aS)-3,4,6,7,9,9a-hexahydro-1H-pyrazino[2,1-c][1,4]oxazin-8-yl]-2-[(3S)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methylpent-2-enenitrile Chemical compound C12=C(N)N=CN=C2N([C@H]2CCCN(C2)C(=O)C(C#N)=CC(C)(C)N2C[C@H]3COCCN3CC2)N=C1C(C(=C1)F)=CC=C1OC1=CC=CC=C1 KVLHSLKAKZYMEZ-UIOOFZCWSA-N 0.000 claims 1
- 208000002205 Allergic Conjunctivitis Diseases 0.000 claims 1
- 206010002198 Anaphylactic reaction Diseases 0.000 claims 1
- 208000003455 Anaphylaxis Diseases 0.000 claims 1
- 206010002556 Ankylosing spondylitis Diseases 0.000 claims 1
- 206010003246 Arthritis Diseases 0.000 claims 1
- 208000003950 B-Cell Lymphoma Diseases 0.000 claims 1
- 210000003719 B-Lymphocytes Anatomy 0.000 claims 1
- 206010073480 B-cell prolymphocytic leukaemia Diseases 0.000 claims 1
- 206010004161 Basedow's disease Diseases 0.000 claims 1
- 208000009137 Behcet Syndrome Diseases 0.000 claims 1
- 201000008335 Behcet's disease Diseases 0.000 claims 1
- 210000004369 Blood Anatomy 0.000 claims 1
- 206010067184 Burkitt's leukaemia Diseases 0.000 claims 1
- YLPIYCASFDJXFO-RUZDIDTESA-N CC(=O)N1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CC(=O)N1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 YLPIYCASFDJXFO-RUZDIDTESA-N 0.000 claims 1
- MURPPFZYZLNBQN-DEOSSOPVSA-N CC(C)(C=C(C#N)C(=O)N1CCC[C@@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCN(CC1)S(C)(=O)=O Chemical compound CC(C)(C=C(C#N)C(=O)N1CCC[C@@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCN(CC1)S(C)(=O)=O MURPPFZYZLNBQN-DEOSSOPVSA-N 0.000 claims 1
- OECSGHDUGHCIMQ-HSZRJFAPSA-N CC(C)(C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CC2(COC2)C1 Chemical compound CC(C)(C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CC2(COC2)C1 OECSGHDUGHCIMQ-HSZRJFAPSA-N 0.000 claims 1
- VZXQFGIJCJMSFZ-HSZRJFAPSA-N CC(C)(C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCNCC1 Chemical compound CC(C)(C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCNCC1 VZXQFGIJCJMSFZ-HSZRJFAPSA-N 0.000 claims 1
- XTBYTIMEUSLGIH-HSZRJFAPSA-N CC(C)(C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CC2(COC2)C1 Chemical compound CC(C)(C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CC2(COC2)C1 XTBYTIMEUSLGIH-HSZRJFAPSA-N 0.000 claims 1
- NOXVOMASUWKHPG-XMMPIXPASA-N CC(C)(C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCN(CC(F)(F)F)CC1 Chemical compound CC(C)(C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCN(CC(F)(F)F)CC1 NOXVOMASUWKHPG-XMMPIXPASA-N 0.000 claims 1
- MURPPFZYZLNBQN-XMMPIXPASA-N CC(C)(C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCN(CC1)S(C)(=O)=O Chemical compound CC(C)(C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCN(CC1)S(C)(=O)=O MURPPFZYZLNBQN-XMMPIXPASA-N 0.000 claims 1
- YDXOXEUWKYKVDD-DEOSSOPVSA-N CC(C)(C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N(C1CC1)C1COC1 Chemical compound CC(C)(C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N(C1CC1)C1COC1 YDXOXEUWKYKVDD-DEOSSOPVSA-N 0.000 claims 1
- OECSGHDUGHCIMQ-QHCPKHFHSA-N CC(C)(C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CC2(COC2)C1 Chemical compound CC(C)(C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CC2(COC2)C1 OECSGHDUGHCIMQ-QHCPKHFHSA-N 0.000 claims 1
- VZXQFGIJCJMSFZ-QHCPKHFHSA-N CC(C)(C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCNCC1 Chemical compound CC(C)(C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12)N1CCNCC1 VZXQFGIJCJMSFZ-QHCPKHFHSA-N 0.000 claims 1
- ULQLAFJMRPZCJZ-JOCHJYFZSA-N CC(C)(NC1COC1)C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CC(C)(NC1COC1)C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 ULQLAFJMRPZCJZ-JOCHJYFZSA-N 0.000 claims 1
- ULQLAFJMRPZCJZ-QFIPXVFZSA-N CC(C)(NC1COC1)C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CC(C)(NC1COC1)C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 ULQLAFJMRPZCJZ-QFIPXVFZSA-N 0.000 claims 1
- BICRABDPLNFWOV-SANMLTNESA-N CC(C)N1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CC(C)N1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 BICRABDPLNFWOV-SANMLTNESA-N 0.000 claims 1
- BICRABDPLNFWOV-AREMUKBSSA-N CC(C)N1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CC(C)N1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 BICRABDPLNFWOV-AREMUKBSSA-N 0.000 claims 1
- FMEWHTMZZYPJGN-HSZRJFAPSA-N CCN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CCN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 FMEWHTMZZYPJGN-HSZRJFAPSA-N 0.000 claims 1
- BYINIOQJRGRANK-QHCPKHFHSA-N CCN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CCN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 BYINIOQJRGRANK-QHCPKHFHSA-N 0.000 claims 1
- OTSKDHVXZWBYCH-RUZDIDTESA-N CCN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CCN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 OTSKDHVXZWBYCH-RUZDIDTESA-N 0.000 claims 1
- CMCZKFPSGLRSEQ-RUZDIDTESA-N CCN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CCN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 CMCZKFPSGLRSEQ-RUZDIDTESA-N 0.000 claims 1
- OTSKDHVXZWBYCH-VWLOTQADSA-N CCN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CCN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 OTSKDHVXZWBYCH-VWLOTQADSA-N 0.000 claims 1
- WBBFEPYVCBJYOO-QFIPXVFZSA-N CN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 WBBFEPYVCBJYOO-QFIPXVFZSA-N 0.000 claims 1
- YELZMARZEBVKBL-JOCHJYFZSA-N CN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 YELZMARZEBVKBL-JOCHJYFZSA-N 0.000 claims 1
- WBBFEPYVCBJYOO-JOCHJYFZSA-N CN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 WBBFEPYVCBJYOO-JOCHJYFZSA-N 0.000 claims 1
- YELZMARZEBVKBL-QFIPXVFZSA-N CN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CN(C1COC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 YELZMARZEBVKBL-QFIPXVFZSA-N 0.000 claims 1
- UAXREQATXBHJAW-XMMPIXPASA-N CN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 UAXREQATXBHJAW-XMMPIXPASA-N 0.000 claims 1
- UAXREQATXBHJAW-DEOSSOPVSA-N CN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 UAXREQATXBHJAW-DEOSSOPVSA-N 0.000 claims 1
- SGXVGVKVFFHVGS-HSZRJFAPSA-N CN1CCN(CC1=O)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound CN1CCN(CC1=O)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 SGXVGVKVFFHVGS-HSZRJFAPSA-N 0.000 claims 1
- NIYAGZIDNIWGFF-AREMUKBSSA-N COCCN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound COCCN1CCN(CC1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 NIYAGZIDNIWGFF-AREMUKBSSA-N 0.000 claims 1
- DEUQAIWVYRNFIH-GIFXNVAJSA-N C[C@H]1CN(C[C@@H](C)N1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound C[C@H]1CN(C[C@@H](C)N1)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 DEUQAIWVYRNFIH-GIFXNVAJSA-N 0.000 claims 1
- ZKIWYNDTGRBYQF-RMTZWNOUSA-N C[C@H]1CN(C[C@@H](C)N1C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 Chemical compound C[C@H]1CN(C[C@@H](C)N1C)C(C)(C)C=C(C#N)C(=O)N1CCC[C@H](C1)n1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc12 ZKIWYNDTGRBYQF-RMTZWNOUSA-N 0.000 claims 1
- 206010008958 Chronic lymphocytic leukaemia Diseases 0.000 claims 1
- 206010009887 Colitis Diseases 0.000 claims 1
- 206010010741 Conjunctivitis Diseases 0.000 claims 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims 1
- 208000005679 Eczema Diseases 0.000 claims 1
- 208000003807 Graves Disease Diseases 0.000 claims 1
- 201000004779 Graves' disease Diseases 0.000 claims 1
- 208000002183 Guillain-Barre Syndrome Diseases 0.000 claims 1
- 206010020751 Hypersensitivity Diseases 0.000 claims 1
- 208000001718 Immediate Hypersensitivity Diseases 0.000 claims 1
- 206010021972 Inflammatory bowel disease Diseases 0.000 claims 1
- 208000001152 Leukemia, Prolymphocytic, B-Cell Diseases 0.000 claims 1
- 206010052178 Lymphocytic lymphoma Diseases 0.000 claims 1
- 206010026798 Mantle cell lymphomas Diseases 0.000 claims 1
- 208000003351 Melanosis Diseases 0.000 claims 1
- LCFFREMLXLZNHE-UHFFFAOYSA-N NC1=C2C(=NC=N1)N(N=C2C1=C(C=C(C=C1)OC1=CC=CC=C1)F)C1CN(CCC1)C(=O)C(C#N)=CC(C)(N1CCN(CC1)C1COC1)C Chemical compound NC1=C2C(=NC=N1)N(N=C2C1=C(C=C(C=C1)OC1=CC=CC=C1)F)C1CN(CCC1)C(=O)C(C#N)=CC(C)(N1CCN(CC1)C1COC1)C LCFFREMLXLZNHE-UHFFFAOYSA-N 0.000 claims 1
- DYVPEYHYUHODQP-FQEVSTJZSA-N NC1=C2C(=NC=N1)N(N=C2C1=C(C=C(C=C1)OC1=CC=CC=C1)F)[C@@H]1CN(CCC1)C(=O)C(C#N)=C(C(C)(C1COC1)C)N Chemical compound NC1=C2C(=NC=N1)N(N=C2C1=C(C=C(C=C1)OC1=CC=CC=C1)F)[C@@H]1CN(CCC1)C(=O)C(C#N)=C(C(C)(C1COC1)C)N DYVPEYHYUHODQP-FQEVSTJZSA-N 0.000 claims 1
- DYVPEYHYUHODQP-HXUWFJFHSA-N NC1=C2C(=NC=N1)N(N=C2C1=C(C=C(C=C1)OC1=CC=CC=C1)F)[C@H]1CN(CCC1)C(=O)C(C#N)=C(C(C)(C1COC1)C)N Chemical compound NC1=C2C(=NC=N1)N(N=C2C1=C(C=C(C=C1)OC1=CC=CC=C1)F)[C@H]1CN(CCC1)C(=O)C(C#N)=C(C(C)(C1COC1)C)N DYVPEYHYUHODQP-HXUWFJFHSA-N 0.000 claims 1
- 206010029592 Non-Hodgkin's lymphomas Diseases 0.000 claims 1
- 208000007452 Plasmacytoma Diseases 0.000 claims 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims 1
- 206010037162 Psoriatic arthropathy Diseases 0.000 claims 1
- 206010039073 Rheumatoid arthritis Diseases 0.000 claims 1
- 206010039085 Rhinitis allergic Diseases 0.000 claims 1
- 206010039710 Scleroderma Diseases 0.000 claims 1
- 206010062113 Splenic marginal zone lymphoma Diseases 0.000 claims 1
- 206010043561 Thrombocytopenic purpura Diseases 0.000 claims 1
- 210000001541 Thymus Gland Anatomy 0.000 claims 1
- 206010045240 Type I hypersensitivity Diseases 0.000 claims 1
- 206010047802 Waldenstrom's macroglobulinaemias Diseases 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 201000005794 allergic hypersensitivity disease Diseases 0.000 claims 1
- 201000010105 allergic rhinitis Diseases 0.000 claims 1
- 150000001408 amides Chemical group 0.000 claims 1
- 230000036783 anaphylactic response Effects 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 229940121363 anti-inflammatory agents Drugs 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 201000009596 autoimmune hypersensitivity disease Diseases 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 230000001684 chronic Effects 0.000 claims 1
- 238000005859 coupling reaction Methods 0.000 claims 1
- 230000003111 delayed Effects 0.000 claims 1
- 201000004624 dermatitis Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drugs Drugs 0.000 claims 1
- 231100001003 eczema Toxicity 0.000 claims 1
- 239000002702 enteric coating Substances 0.000 claims 1
- 238000009505 enteric coating Methods 0.000 claims 1
- 201000003444 follicular lymphoma Diseases 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 238000005469 granulation Methods 0.000 claims 1
- 230000003179 granulation Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 201000007919 lymphoplasmacytic lymphoma Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 201000006417 multiple sclerosis Diseases 0.000 claims 1
- 150000002829 nitrogen Chemical group 0.000 claims 1
- 201000001263 psoriatic arthritis Diseases 0.000 claims 1
- 238000002054 transplantation Methods 0.000 claims 1
- 230000009959 type I hypersensitivity Effects 0.000 claims 1
- VJZPVXUYSVSYMH-HEGSZGHRSA-N CCCC(/C=C(/C(N(CCC1)C[C@@H]1[n](c1ncnc(N)c11)nc1-c(c(F)c1)ccc1Oc1ccccc1)=O)\C#N)N1CCNCC1 Chemical compound CCCC(/C=C(/C(N(CCC1)C[C@@H]1[n](c1ncnc(N)c11)nc1-c(c(F)c1)ccc1Oc1ccccc1)=O)\C#N)N1CCNCC1 VJZPVXUYSVSYMH-HEGSZGHRSA-N 0.000 description 1
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261699038P | 2012-09-10 | 2012-09-10 | |
US61/699,038 | 2012-09-10 | ||
US201261728693P | 2012-11-20 | 2012-11-20 | |
US61/728,693 | 2012-11-20 | ||
US201361782605P | 2013-03-14 | 2013-03-14 | |
US61/782,605 | 2013-03-14 | ||
PCT/US2013/058614 WO2014039899A1 (en) | 2012-09-10 | 2013-09-06 | Pyrazolopyrimidine compounds as kinase inhibitors |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2015527401A JP2015527401A (ja) | 2015-09-17 |
JP2015527401A5 true JP2015527401A5 (zh) | 2016-10-20 |
JP6203848B2 JP6203848B2 (ja) | 2017-09-27 |
Family
ID=49170940
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015531259A Active JP6203848B2 (ja) | 2012-09-10 | 2013-09-06 | キナーゼ阻害剤としてのピラゾロピリミジン化合物 |
Country Status (27)
Country | Link |
---|---|
US (7) | US9266895B2 (zh) |
EP (2) | EP3181567B1 (zh) |
JP (1) | JP6203848B2 (zh) |
KR (1) | KR102203990B1 (zh) |
CN (1) | CN104822681B (zh) |
AU (1) | AU2013312296B2 (zh) |
BR (1) | BR112015003859B1 (zh) |
CA (1) | CA2882367C (zh) |
CY (1) | CY1122611T1 (zh) |
DK (1) | DK3181567T3 (zh) |
EA (1) | EA027213B9 (zh) |
ES (2) | ES2731833T3 (zh) |
HK (1) | HK1211942A1 (zh) |
HR (2) | HRP20171601T1 (zh) |
HU (1) | HUE044146T2 (zh) |
IL (2) | IL237285B (zh) |
LT (1) | LT3181567T (zh) |
ME (1) | ME03455B (zh) |
MX (1) | MX361815B (zh) |
NZ (1) | NZ630925A (zh) |
PL (2) | PL3181567T3 (zh) |
PT (2) | PT2892900T (zh) |
RS (1) | RS58956B1 (zh) |
SG (1) | SG11201501815UA (zh) |
SI (2) | SI3181567T1 (zh) |
WO (1) | WO2014039899A1 (zh) |
ZA (1) | ZA201501615B (zh) |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9376438B2 (en) | 2011-05-17 | 2016-06-28 | Principia Biopharma, Inc. | Pyrazolopyrimidine derivatives as tyrosine kinase inhibitors |
ES2731833T3 (es) | 2012-09-10 | 2019-11-19 | Principia Biopharma Inc | Compuestos pirazolopirimidínicos comos inhibidores de cinasas |
JP6504548B2 (ja) * | 2014-02-21 | 2019-04-24 | プリンシピア バイオファーマ インコーポレイテッド | Btk阻害剤の塩および固体形態 |
CN105017256A (zh) | 2014-04-29 | 2015-11-04 | 浙江导明医药科技有限公司 | 多氟化合物作为布鲁顿酪氨酸激酶抑制剂 |
US10485797B2 (en) | 2014-12-18 | 2019-11-26 | Principia Biopharma Inc. | Treatment of pemphigus |
CA2971109A1 (en) * | 2014-12-24 | 2016-06-30 | Principia Biopharma Inc. | Site specific dosing of a btk inhibitor |
PL3236943T3 (pl) * | 2014-12-24 | 2023-05-29 | Principia Biopharma Inc. | Kompozycje do krętniczo-czczego dostarczania leków |
US9717745B2 (en) | 2015-03-19 | 2017-08-01 | Zhejiang DTRM Biopharma Co. Ltd. | Pharmaceutical compositions and their use for treatment of cancer and autoimmune diseases |
MA41828A (fr) * | 2015-03-27 | 2018-01-30 | Pharmacyclics Llc | Co-cristaux d'un inhibiteur de la tyrosine kinase de bruton |
UA124090C2 (uk) * | 2015-06-03 | 2021-07-21 | Прінсіпіа Байофарма Інк. | Інгібітори тирозинкінази |
MA42242A (fr) | 2015-06-24 | 2018-05-02 | Principia Biopharma Inc | Inhibiteurs de la tyrosine kinase |
BR112018077503A2 (pt) * | 2016-06-29 | 2019-04-09 | Principia Biopharma Inc. | formulações de liberação modificada de 2-[3-[4-amino-3-(2-fluoro-4- fenoxi-fenil)pirazolo [3,4-d]pirimidin-1-il]piperidino-1- carbonil]-4-metil-4-[4-(oxetan-3-il)piperazin-1-il] pent-2-enenitrila |
CN106279284A (zh) * | 2016-08-08 | 2017-01-04 | 上海孚璞生物科技有限公司 | 三取代膦亚胺类化合物及其制备方法、用途 |
CN108101905A (zh) * | 2016-11-24 | 2018-06-01 | 中国科学院上海药物研究所 | 嘧啶并[5,4-b]吲嗪或嘧啶并[5,4-b]吡呤化合物、其制备方法及用途 |
CA3071405A1 (en) * | 2017-08-01 | 2019-02-07 | Recurium Ip Holdings, Llc | 1, 2 - dihydro- 3h- pyrazolo [3, 4 - d] pyrimidin -3 - one analogs |
TW201922256A (zh) | 2017-10-27 | 2019-06-16 | 中國大陸商浙江導明醫藥科技有限公司 | 治療淋巴樣惡性疾病之方法 |
US20210113568A1 (en) | 2018-04-27 | 2021-04-22 | Ono Pharmaceutical Co., Ltd. | PREVENTIVE AND/OR THERAPEUTIC AGENT FOR AUTOIMMUNE DISEASE COMPRISING COMPOUND HAVING Btk INHIBITORY ACTIVITY AS ACTIVE INGREDIENT |
MA53388A (fr) | 2018-07-25 | 2021-06-02 | Novartis Ag | Inhibiteurs d'inflammasome nlrp3 |
CN117285467A (zh) | 2018-07-31 | 2023-12-26 | 罗索肿瘤学公司 | 喷雾干燥的分散体和制剂 |
CA3129665A1 (en) | 2019-03-21 | 2020-09-24 | Onxeo | A dbait molecule in combination with kinase inhibitor for the treatment of cancer |
AR119731A1 (es) | 2019-05-17 | 2022-01-05 | Novartis Ag | Inhibidores del inflamasoma nlrp3 |
KR20220079909A (ko) | 2019-10-09 | 2022-06-14 | 프린시피아 바이오파마, 인코퍼레이티드 | (R)-2-[3-[4-아미노-3-(2-플루오로-4-페녹시-페닐)피라졸로[3,4-d]피리미딘-1-일]피페리딘-1-카르보닐]-4-메틸-4-[4-(옥세탄-3-일)피페라진-1-일]펜트-2-엔니트릴을 투여하여 천포창을 치료하는 방법 |
WO2021076514A1 (en) | 2019-10-14 | 2021-04-22 | Principia Biopharma Inc. | Methods for treating immune thrombocytopenia by administering (r)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile |
CN114761006A (zh) | 2019-11-08 | 2022-07-15 | Inserm(法国国家健康医学研究院) | 对激酶抑制剂产生耐药性的癌症的治疗方法 |
JP2023507125A (ja) * | 2019-12-20 | 2023-02-21 | プリンシピア バイオファーマ インコーポレイテッド | 2-[3-[4-アミノ-3-(2-フルオロ-4-フェノキシ-フェニル)ピラゾロ[3,4-d]ピリミジン-1-イル]ピペリジン-1-カルボニル]-4-メチル-4-[4-(オキセタン-3-イル)ピペラジン-1-イル]ペント-2-エンニトリルの固体形態 |
US11583533B2 (en) | 2020-01-08 | 2023-02-21 | Principia Biopharma Inc. | Topical pharmaceutical compositions comprising 2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile |
KR20220130179A (ko) | 2020-01-20 | 2022-09-26 | 젠자임 코포레이션 | 재발성 다발성 경화증(rms)에 대한 치료용 티로신 키나제 저해제 |
WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
IL294785A (en) * | 2020-01-22 | 2022-09-01 | Principia Biopharma Inc | Crystal forms of 2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)-1h-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]- 4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile |
KR20230015346A (ko) | 2020-04-22 | 2023-01-31 | 프린시피아 바이오파마, 인코퍼레이티드 | Btk 억제제를 사용하는 급성 호흡 곤란 증후군 및 시토카인 폭풍을 수반하는 다른 장애의 치료 |
US11708366B2 (en) | 2020-08-14 | 2023-07-25 | Novartis Ag | Heteroaryl substituted spiropiperidinyl derivatives and pharmaceutical uses thereof |
JP2023553930A (ja) | 2020-12-10 | 2023-12-26 | ジェンザイム・コーポレーション | トレブルチニブの結晶形態、その製造方法、およびその使用 |
WO2022140246A1 (en) | 2020-12-21 | 2022-06-30 | Hangzhou Jijing Pharmaceutical Technology Limited | Methods and compounds for targeted autophagy |
EP4313023A1 (en) | 2021-04-02 | 2024-02-07 | Biogen MA Inc. | Combination treatment methods of multiple sclerosis |
KR20230171975A (ko) | 2021-04-16 | 2023-12-21 | 프린시피아 바이오파마, 인코퍼레이티드 | 특정 화합물을 투여하여 약물 및 백신 유발성 면역성 혈소판 감소증을 치료하는 방법 |
WO2023244562A1 (en) | 2022-06-14 | 2023-12-21 | Principia Biopharma Inc. | Crystalline forms of 2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1- yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile |
WO2023249980A1 (en) * | 2022-06-22 | 2023-12-28 | Genzyme Corporation | Methods of making modified btk inhibitors |
US20240067627A1 (en) | 2022-08-03 | 2024-02-29 | Novartis Ag | Nlrp3 inflammasome inhibitors |
WO2024097667A1 (en) | 2022-10-31 | 2024-05-10 | Principia Biopharma Inc. | Methods for treating immune thrombocytopenia by administering (r)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-l-yl]piperidine-l-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-l-yl]pent-2-enenitrile |
WO2024124113A1 (en) | 2022-12-09 | 2024-06-13 | Principia Biopharma Inc. | Methods for treating immune thrombocytopenia in subjects with cognitive impairment by administering rilzabrutinib |
Family Cites Families (127)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS428308Y1 (zh) | 1964-09-09 | 1967-04-27 | ||
US4107288A (en) | 1974-09-18 | 1978-08-15 | Pharmaceutical Society Of Victoria | Injectable compositions, nanoparticles useful therein, and process of manufacturing same |
US4082819A (en) | 1977-03-02 | 1978-04-04 | The Standard Oil Company | Rubber-modified acrylonitrile-vinyl ether-indene polymers |
JPS5617367A (en) | 1979-07-23 | 1981-02-19 | Fuji Xerox Co Ltd | Magnetic brush developing unit |
JPS5663950A (en) | 1979-10-30 | 1981-05-30 | Mitsubishi Chem Ind Ltd | Cyclopropanecarboxylic ester |
FR2535721A1 (fr) | 1982-11-08 | 1984-05-11 | Sanofi Sa | Derives de la piperidinedione protecteurs du myocarde presentant une acticite antiarythmique, leur procede de preparation et les medicaments qui contiennent lesdits derives |
US4476116A (en) | 1982-12-10 | 1984-10-09 | Syntex (U.S.A.) Inc. | Polypeptides/chelating agent nasal compositions having enhanced peptide absorption |
US5116817A (en) | 1982-12-10 | 1992-05-26 | Syntex (U.S.A.) Inc. | LHRH preparations for intranasal administration |
US4911920A (en) | 1986-07-30 | 1990-03-27 | Alcon Laboratories, Inc. | Sustained release, comfort formulation for glaucoma therapy |
JPS623848A (ja) | 1985-06-28 | 1987-01-09 | Nippon Steel Corp | 疲労強度のすぐれたスタツド付きフラツシユバツト溶接アンカ−チエ−ン |
FR2588189B1 (fr) | 1985-10-03 | 1988-12-02 | Merck Sharp & Dohme | Composition pharmaceutique de type a transition de phase liquide-gel |
JPH0731201B2 (ja) | 1987-12-31 | 1995-04-10 | トロピックス・インコーポレーテッド | 化学発光による測定法 |
JP2518353B2 (ja) | 1988-06-09 | 1996-07-24 | 住友化学工業株式会社 | シアノ酢酸アミド誘導体およびその製造中間体 |
CA2018801C (en) | 1990-06-12 | 2000-08-22 | Pierre Louis Beaulieu | Antiherpes peptide derivatives having a 1,4-dioxo c n-terminus |
JPH04177244A (ja) | 1990-11-10 | 1992-06-24 | Konica Corp | ハロゲン化銀写真感光材料 |
CA2033447C (en) | 1990-12-31 | 1999-08-31 | Robert Deziel | Synergistic combination for treating herpes infections |
DK0495421T3 (da) | 1991-01-15 | 1996-12-09 | Alcon Lab Inc | Anvendelse af carragenaner i topiske ophthalmiske sammensætninger |
US5145684A (en) | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
US5212162A (en) | 1991-03-27 | 1993-05-18 | Alcon Laboratories, Inc. | Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions |
JPH05301838A (ja) | 1991-10-15 | 1993-11-16 | Mitsubishi Kasei Corp | スチレン誘導体 |
US5792771A (en) | 1992-11-13 | 1998-08-11 | Sugen, Inc. | Quinazoline compounds and compositions thereof for the treatment of disease |
WO1995024190A2 (en) | 1994-03-07 | 1995-09-14 | Sugen, Inc. | Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof |
JPH0827090A (ja) | 1994-05-13 | 1996-01-30 | Sumitomo Chem Co Ltd | シアノ酢酸アミド誘導体、その用途およびその製造中間体 |
US6331555B1 (en) * | 1995-06-01 | 2001-12-18 | University Of California | Treatment of platelet derived growth factor related disorders such as cancers |
KR20000076192A (ko) | 1997-03-14 | 2000-12-26 | 스타르크, 카르크 | 시클로알킬알칸카르복사미드 및 그의 제조 방법 및 용도 |
US7863444B2 (en) | 1997-03-19 | 2011-01-04 | Abbott Laboratories | 4-aminopyrrolopyrimidines as kinase inhibitors |
US6391452B1 (en) | 1997-07-18 | 2002-05-21 | Bayer Corporation | Compositions for nasal drug delivery, methods of making same, and methods of removing residual solvent from pharmaceutical preparations |
IL125947A0 (en) | 1997-09-17 | 1999-04-11 | American Cyanamid Co | 3-(1,2-benzisothiazol- and isoxazol-5-yl)-2,4(1h,3h)-pyrimidinedione or thione and 3-(1,2-benzisothiazol- and isoxazol-5-yl)-4(3)-pyrimidinone or thione herbicidal agents |
US6713474B2 (en) | 1998-09-18 | 2004-03-30 | Abbott Gmbh & Co. Kg | Pyrrolopyrimidines as therapeutic agents |
RU2260592C9 (ru) | 1999-04-15 | 2017-04-07 | Бристол-Маерс Сквибб Ко. | Циклические ингибиторы протеинтирозинкиназ |
SK3812002A3 (en) | 1999-09-17 | 2003-09-11 | Abbott Gmbh & Co Kg | Pyrazolopyrimidines as therapeutic agents |
WO2001072751A1 (en) | 2000-03-29 | 2001-10-04 | Knoll Gesellschaft Mit Beschraenkter Haftung | Pyrrolopyrimidines as tyrosine kinase inhibitors |
AR042586A1 (es) | 2001-02-15 | 2005-06-29 | Sugen Inc | 3-(4-amidopirrol-2-ilmetiliden)-2-indolinona como inhibidores de la protein quinasa; sus composiciones farmaceuticas; un metodo para la modulacion de la actividad catalitica de la proteinquinasa; un metodo para tratar o prevenir una afeccion relacionada con la proteinquinasa |
MXPA03008560A (es) * | 2001-03-22 | 2004-06-30 | Abbot Gmbh & Co Kg | Pirazolopirimidinas como agentes terapeuticos. |
CA2465328C (en) | 2001-11-01 | 2011-06-14 | Michael Francis Gross | Piperidines |
JP3991812B2 (ja) | 2001-12-11 | 2007-10-17 | 住友化学株式会社 | エステル化合物およびその用途 |
WO2003068157A2 (en) | 2002-02-11 | 2003-08-21 | The Brigham And Women's Hospital, Inc. | Kinase inhibitors and methods of use thereof |
NI200300043A (es) | 2002-03-28 | 2003-11-05 | Warner Lambert Co | AMINOACIDOS CON AFINIDAD POR LA PROTEINA a2DELTA. |
GB0219024D0 (en) | 2002-08-15 | 2002-09-25 | Pfizer Ltd | Synergistic combinations |
US7419981B2 (en) | 2002-08-15 | 2008-09-02 | Pfizer Inc. | Synergistic combinations of an alpha-2-delta ligand and a cGMP phosphodieterse 5 inhibitor |
GB0226370D0 (en) | 2002-11-12 | 2002-12-18 | Novartis Ag | Organic compounds |
WO2004074283A1 (en) | 2003-02-21 | 2004-09-02 | Pfizer Inc. | N-heterocyclyl-substituted amino-thiazole derivatives as protein kinase inhibitors |
US20050008640A1 (en) | 2003-04-23 | 2005-01-13 | Wendy Waegell | Method of treating transplant rejection |
WO2005011812A1 (en) | 2003-08-01 | 2005-02-10 | Chugai Seiyaku Kabushiki Kaisha | Cyanoamide compounds useful as malonyl-coa decarboxylase inhibithors |
WO2005023773A1 (en) | 2003-09-04 | 2005-03-17 | Pfizer Limited | Process for the preparation of substituted aryl pyrazoles |
GB0322140D0 (en) | 2003-09-22 | 2003-10-22 | Pfizer Ltd | Combinations |
BRPI0414798A (pt) | 2003-09-25 | 2006-11-21 | Warner Lambert Co | métodos para usar aminoácidos com afinidade para a proteìna alfa2delta |
US20060025383A1 (en) | 2004-02-03 | 2006-02-02 | Neil Wishart | Aminobenzoxazoles as therapeutic agents |
JP4552456B2 (ja) | 2004-02-27 | 2010-09-29 | 住友化学株式会社 | エステル化合物およびその用途 |
US20070197510A1 (en) | 2004-03-10 | 2007-08-23 | Kazuyuki Ohmoto | Nitriles and medicinal compositions containing the same as the active ingredient |
US7807719B2 (en) | 2004-09-14 | 2010-10-05 | Chaim Roifman | Compounds useful for modulating abnormal cell proliferation |
US20060079494A1 (en) * | 2004-09-27 | 2006-04-13 | Santi Daniel V | Specific kinase inhibitors |
CA2597587A1 (en) | 2005-02-11 | 2006-08-17 | Coley Pharmaceutical Group, Inc. | Oxime and hydroxylamine substituted imidazo[4,5-c] ring compounds and methods |
AU2006228525A1 (en) | 2005-03-28 | 2006-10-05 | Dexcel Pharma Technologies Ltd. | Controlled absorption of statins in the intestine |
MX2007015216A (es) | 2005-06-03 | 2008-02-22 | Xenon Pharmaceuticals Inc | Derivados de aminotiazol y sus usos como agentes terapeuticos. |
ATE456557T1 (de) | 2005-06-15 | 2010-02-15 | Pfizer Ltd | Substituierte arylpyrazole zur verwendung gegen parasiten |
US20070149464A1 (en) | 2005-06-15 | 2007-06-28 | Pfizer Inc. | Combination |
US20080176865A1 (en) | 2005-06-15 | 2008-07-24 | Pfizer Limited | Substituted arylpyrazoles |
US20080146643A1 (en) | 2005-06-15 | 2008-06-19 | Pfizer Limited | Combination |
US7645786B2 (en) | 2005-06-15 | 2010-01-12 | Pfizer Inc. | Substituted arylpyrazoles |
CN101282936B (zh) | 2005-10-07 | 2012-05-16 | 橘生药品工业株式会社 | 氮化杂环化合物及包含其的药物组合物 |
JP5193876B2 (ja) | 2005-12-02 | 2013-05-08 | バイエル・ヘルスケア・エルエルシー | オーロラキナーゼの阻害により癌を処置するために有用なピロロトリアジン誘導体 |
BRPI0621027A2 (pt) | 2006-01-13 | 2011-11-29 | Pharmacyclics Inc | composto, composição farmacêutica |
ES2533383T3 (es) | 2006-03-31 | 2015-04-09 | The Board Of Regents Of The University Of Texas System | Fármacos anticancerosos biodisponibles por vía oral relacionados con ácido cafeico |
US7645748B2 (en) | 2006-04-03 | 2010-01-12 | Forbes Medi-Tech Inc. | Sterol/stanol phosphorylnitroderivatives and use thereof |
US8846697B2 (en) | 2006-05-31 | 2014-09-30 | The Regents Of The University Of California | Purine analogs |
US20100292229A1 (en) * | 2006-06-30 | 2010-11-18 | The Board Of Regents Of The University Of Texas System | Tryphostin-analogs for the treatment of cell proliferative diseases |
EP2049500B1 (en) | 2006-07-06 | 2011-09-07 | Array Biopharma, Inc. | Cyclopenta [d] pyrimidines as akt protein kinase inhibitors |
EP2532235A1 (en) | 2006-09-22 | 2012-12-12 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase |
ES2403546T3 (es) | 2006-11-03 | 2013-05-20 | Pharmacyclics, Inc. | Sonda de actividad de la tirosina-cinasa de Bruton y procedimiento de utilización |
AU2007323335A1 (en) | 2006-11-23 | 2008-05-29 | Novartis Ag | Pyrimidines and their use as CXCR2 receptor antagonists |
EP2125819B1 (en) | 2007-03-21 | 2014-10-22 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful for the treatment of proliferative, allergic, autoimmune or inflammatory diseases |
GB2447933A (en) | 2007-03-27 | 2008-10-01 | Chemence Ltd | Cyanoacrylate monomer for forming an adhesive polymer |
MX2009010284A (es) | 2007-03-28 | 2010-01-29 | Pharmacyclics Inc | Inhibidores de la tirosina-cinasa de bruton. |
CA2712507A1 (en) | 2008-02-25 | 2009-09-03 | F. Hoffmann-La Roche Ag | Pyrrolopyrazine kinase inhibitors |
PL2247592T3 (pl) | 2008-02-25 | 2012-01-31 | Hoffmann La Roche | Pirolopirazynowe inhibitory kinazy |
WO2009140128A2 (en) | 2008-05-13 | 2009-11-19 | Irm Llc | Compounds and compositions as kinase inhibitors |
US8691838B2 (en) | 2008-05-22 | 2014-04-08 | Amgen Inc. | Heterocycles as protein kinase inhibitors |
EP2289273A4 (en) | 2008-06-19 | 2013-11-13 | Ericsson Telefon Ab L M | PREDICTION OF BIT RATE |
EP3311818A3 (en) * | 2008-07-16 | 2018-07-18 | Pharmacyclics, LLC | Inhibitors of bruton's tyrosine kinase for the treatment of solid tumors |
CA2732628A1 (en) | 2008-08-01 | 2010-02-04 | Biocryst Pharmaceuticals, Inc. | Therapeutic agents |
US8450337B2 (en) * | 2008-09-30 | 2013-05-28 | Moleculin, Llc | Methods of treating skin disorders with caffeic acid analogs |
US20100113520A1 (en) | 2008-11-05 | 2010-05-06 | Principia Biopharma, Inc. | Kinase knockdown via electrophilically enhanced inhibitors |
US20120028981A1 (en) | 2008-11-05 | 2012-02-02 | Principia Biopharma Inc. | Kinase Knockdown Via Electrophilically Enhanced Inhibitors |
US8426428B2 (en) | 2008-12-05 | 2013-04-23 | Principia Biopharma, Inc. | EGFR kinase knockdown via electrophilically enhanced inhibitors |
CA2773848A1 (en) | 2009-09-09 | 2011-03-17 | Avila Therapeutics, Inc. | Pi3 kinase inhibitors and uses thereof |
US7741330B1 (en) | 2009-10-12 | 2010-06-22 | Pharmacyclics, Inc. | Pyrazolo-pyrimidine inhibitors of Bruton's tyrosine kinase |
AU2010319964A1 (en) | 2009-11-16 | 2012-06-07 | The Regents Of The University Of California | Kinase inhibitors |
CA2799904A1 (en) | 2010-05-20 | 2011-11-24 | F. Hoffmann-La Roche Ag | Pyrrolo [2, 3 - b] pyrazine - 7 - carboxamide derivatives and their use as jak and syk inhibitors |
MY189483A (en) | 2010-05-31 | 2022-02-16 | Ono Pharmaceutical Co | Purinone derivative |
MX2020004501A (es) | 2010-06-03 | 2021-11-09 | Pharmacyclics Llc | El uso de inhibidores de la tirosina quinasa de bruton (btk). |
US20120071497A1 (en) | 2010-06-03 | 2012-03-22 | Pharmacyclics, Inc. | Methods of treating abc-dlbcl using inhibitors of bruton's tyrosine kinase |
CN101880243A (zh) | 2010-06-04 | 2010-11-10 | 贵阳柏丝特化工有限公司 | 一种含氟氰拟除虫菊酯化合物及其合成方法与用途 |
CN103096716B (zh) | 2010-08-10 | 2016-03-02 | 西建阿维拉米斯研究公司 | Btk抑制剂的苯磺酸盐 |
US9376438B2 (en) | 2011-05-17 | 2016-06-28 | Principia Biopharma, Inc. | Pyrazolopyrimidine derivatives as tyrosine kinase inhibitors |
PT2710005T (pt) | 2011-05-17 | 2016-11-16 | Principia Biopharma Inc | Inibidores de tirosina-quinase |
WO2012158810A1 (en) | 2011-05-17 | 2012-11-22 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
EP2710007B1 (en) | 2011-05-17 | 2019-12-11 | The Regents of The University of California | Kinase inhibitors |
WO2013003629A2 (en) | 2011-06-28 | 2013-01-03 | Pharmacyclics, Inc. | Methods and compositions for inhibition of bone resorption |
CA2841080A1 (en) | 2011-07-13 | 2013-01-17 | Pharmacyclics, Inc. | Inhibitors of bruton's tyrosine kinase |
EP2548877A1 (en) | 2011-07-19 | 2013-01-23 | MSD Oss B.V. | 4-(5-Membered fused pyridinyl)benzamides as BTK-inhibitors |
AU2012285988B2 (en) | 2011-07-19 | 2017-05-25 | Merck Sharp & Dohme B.V. | 4-imidazopyridazin-1-yl-benzamides and 4-imidazotriazin-1-yl-benzamides Btk-inhibitors |
ES2708224T3 (es) | 2011-07-19 | 2019-04-09 | Merck Sharp & Dohme | 4-Imidazopiridazín-1-il-benzamidas y 4-imidazotriazín-1-il-benzamidas como inhibidores de Btk |
CN103874699A (zh) | 2011-09-20 | 2014-06-18 | 赛尔佐姆有限公司 | 吡唑并[4,3-c]吡啶衍生物作为激酶抑制剂 |
KR102054468B1 (ko) | 2011-10-19 | 2019-12-11 | 파마싸이클릭스 엘엘씨 | 브루톤 티로신 인산화효소(btk)의 억제제의 용도 |
US8377946B1 (en) | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
US8501724B1 (en) | 2012-01-31 | 2013-08-06 | Pharmacyclics, Inc. | Purinone compounds as kinase inhibitors |
EP2858500A4 (en) | 2012-06-08 | 2016-04-06 | Biogen Ma Inc | INHIBITORS OF BRUTON TYROSINE KINASE |
DK2861599T3 (da) | 2012-06-18 | 2020-03-02 | Principia Biopharma Inc | Reversible kovalente pyrrolo- eller pyrazolopyrimidiner, der er nyttige til behandling af cancer og autoimmunsygdomme |
US20150140085A1 (en) | 2012-06-29 | 2015-05-21 | Principia Biopharma Inc. | Formulations comprising ibrutinib |
US9572811B2 (en) | 2012-08-03 | 2017-02-21 | Principia Biopharma Inc. | Treatment of dry eye |
ES2731833T3 (es) | 2012-09-10 | 2019-11-19 | Principia Biopharma Inc | Compuestos pirazolopirimidínicos comos inhibidores de cinasas |
US20150291554A1 (en) | 2012-11-02 | 2015-10-15 | Pfizer Inc. | Bruton's Tyrosine Kinase Inhibitors |
JP2015537033A (ja) | 2012-11-15 | 2015-12-24 | ファーマサイクリックス,インク. | キナーゼ阻害剤としてのピロロピリミジン化合物 |
US20140142099A1 (en) | 2012-11-20 | 2014-05-22 | Principia Biopharma Inc. | Purinone Derivatives as Tyrosine Kinase Inhibitors |
JO3377B1 (ar) | 2013-03-11 | 2019-03-13 | Takeda Pharmaceuticals Co | مشتقات بيريدينيل وبيريدينيل مندمج |
US8957080B2 (en) | 2013-04-09 | 2015-02-17 | Principia Biopharma Inc. | Tyrosine kinase inhibitors |
JP6162904B2 (ja) | 2014-02-03 | 2017-07-12 | カディラ ヘルスケア リミティド | 新規複素環式化合物 |
JP6504548B2 (ja) | 2014-02-21 | 2019-04-24 | プリンシピア バイオファーマ インコーポレイテッド | Btk阻害剤の塩および固体形態 |
US10485797B2 (en) | 2014-12-18 | 2019-11-26 | Principia Biopharma Inc. | Treatment of pemphigus |
CA2971109A1 (en) | 2014-12-24 | 2016-06-30 | Principia Biopharma Inc. | Site specific dosing of a btk inhibitor |
PL3236943T3 (pl) | 2014-12-24 | 2023-05-29 | Principia Biopharma Inc. | Kompozycje do krętniczo-czczego dostarczania leków |
UA124090C2 (uk) | 2015-06-03 | 2021-07-21 | Прінсіпіа Байофарма Інк. | Інгібітори тирозинкінази |
MA42242A (fr) | 2015-06-24 | 2018-05-02 | Principia Biopharma Inc | Inhibiteurs de la tyrosine kinase |
CN105753863B (zh) | 2015-09-11 | 2018-07-31 | 东莞市真兴贝特医药技术有限公司 | 氧代二氢咪唑并吡啶类化合物及其应用 |
CA3008653A1 (en) | 2015-10-14 | 2017-04-20 | Zibo Biopolar Changsheng Pharmaceutical Co. Ltd. | Bruton's tyrosine kinase inhibitors |
BR112018077503A2 (pt) | 2016-06-29 | 2019-04-09 | Principia Biopharma Inc. | formulações de liberação modificada de 2-[3-[4-amino-3-(2-fluoro-4- fenoxi-fenil)pirazolo [3,4-d]pirimidin-1-il]piperidino-1- carbonil]-4-metil-4-[4-(oxetan-3-il)piperazin-1-il] pent-2-enenitrila |
-
2013
- 2013-09-06 ES ES17152898T patent/ES2731833T3/es active Active
- 2013-09-06 SI SI201331490T patent/SI3181567T1/sl unknown
- 2013-09-06 PT PT137627030T patent/PT2892900T/pt unknown
- 2013-09-06 PL PL17152898T patent/PL3181567T3/pl unknown
- 2013-09-06 BR BR112015003859-0A patent/BR112015003859B1/pt active IP Right Grant
- 2013-09-06 PT PT17152898T patent/PT3181567T/pt unknown
- 2013-09-06 EP EP17152898.7A patent/EP3181567B1/en active Active
- 2013-09-06 NZ NZ630925A patent/NZ630925A/en unknown
- 2013-09-06 EP EP13762703.0A patent/EP2892900B1/en active Active
- 2013-09-06 SI SI201330822T patent/SI2892900T1/en unknown
- 2013-09-06 CN CN201380046810.4A patent/CN104822681B/zh active Active
- 2013-09-06 SG SG11201501815UA patent/SG11201501815UA/en unknown
- 2013-09-06 EA EA201590230A patent/EA027213B9/ru not_active IP Right Cessation
- 2013-09-06 ES ES13762703.0T patent/ES2644964T3/es active Active
- 2013-09-06 JP JP2015531259A patent/JP6203848B2/ja active Active
- 2013-09-06 AU AU2013312296A patent/AU2013312296B2/en active Active
- 2013-09-06 RS RS20190691A patent/RS58956B1/sr unknown
- 2013-09-06 KR KR1020157008939A patent/KR102203990B1/ko active IP Right Grant
- 2013-09-06 US US14/374,788 patent/US9266895B2/en active Active
- 2013-09-06 ME MEP-2019-164A patent/ME03455B/me unknown
- 2013-09-06 MX MX2015002955A patent/MX361815B/es active IP Right Grant
- 2013-09-06 DK DK17152898.7T patent/DK3181567T3/da active
- 2013-09-06 PL PL13762703T patent/PL2892900T3/pl unknown
- 2013-09-06 WO PCT/US2013/058614 patent/WO2014039899A1/en active Application Filing
- 2013-09-06 LT LTEP17152898.7T patent/LT3181567T/lt unknown
- 2013-09-06 CA CA2882367A patent/CA2882367C/en active Active
- 2013-09-06 HU HUE17152898A patent/HUE044146T2/hu unknown
-
2014
- 2014-08-20 US US14/464,602 patent/US8940744B2/en active Active
-
2015
- 2015-02-17 IL IL237285A patent/IL237285B/en active IP Right Grant
- 2015-03-10 ZA ZA2015/01615A patent/ZA201501615B/en unknown
-
2016
- 2016-01-05 HK HK16100044.8A patent/HK1211942A1/zh unknown
- 2016-01-15 US US14/997,330 patent/US9994576B2/en active Active
-
2017
- 2017-10-19 HR HRP20171601TT patent/HRP20171601T1/hr unknown
-
2018
- 2018-05-11 US US15/978,041 patent/US10533013B2/en active Active
-
2019
- 2019-02-24 IL IL26500719A patent/IL265007B/en active IP Right Grant
- 2019-06-19 CY CY20191100638T patent/CY1122611T1/el unknown
- 2019-06-19 HR HRP20191126TT patent/HRP20191126T1/hr unknown
- 2019-12-09 US US16/708,340 patent/US11040980B2/en active Active
-
2021
- 2021-05-19 US US17/324,674 patent/US20220073522A1/en not_active Abandoned
-
2023
- 2023-06-29 US US18/344,167 patent/US20240174676A1/en active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2015527401A5 (zh) | ||
US10980815B2 (en) | Aminopyrimidinyl compounds | |
EA027213B1 (ru) | Соединения пиразолопиримидина в качестве ингибиторов киназ | |
HRP20170017T1 (hr) | Inhibitori tirozin kinaze | |
US7834039B2 (en) | Oxadiazole compounds | |
US9783552B2 (en) | Soluble guanylate cyclase activators | |
WO2018092089A1 (en) | Heterocyclic amides as kinase inhibitors | |
JP2015501327A5 (zh) | ||
JP2015514056A5 (zh) | ||
TW200835481A (en) | Imidazotriazines and imidazopyrimidines as kinase inhibitors | |
CN1520298A (zh) | 作为治疗剂的吡唑并嘧啶类 | |
WO2009023269A3 (en) | 4-(9-(3, 3-difluorocyclopentyl) -5, 7, 7-trimethyl-6-oxo-6, 7, 8, 9-tetrahydro-5h-pyrimido [4, 5-b[1, 4] diazepin-2-ylamino)-3-methoxybenzamide derivatives as inhibitors of the human protein kinases plk1 to plk4 for the treatment of proliferative diseases | |
WO2019224773A1 (en) | Heterocyclic amides as rip1 kinase inhibitors | |
EP3732176A1 (en) | Heterocyclic amides as kinase inhibitors | |
EP3668858A1 (en) | Pyrazolo[1,5-a]pyrazin-4-yl and related derivatives | |
JPWO2016204153A1 (ja) | 置換ジヒドロピロロピラゾール誘導体 | |
JP2021500340A5 (zh) | ||
JP2020536915A5 (zh) | ||
JP2016539993A5 (zh) | ||
CA2837248A1 (en) | Novel phthalazinone -pyrrolopyrimidinecarboxamide derivatives | |
JP2018510192A5 (zh) | ||
CN101291582A (zh) | 以咪唑为基础的新杂环化合物 | |
BR112017026994B1 (pt) | Composto, e, composição farmacêutica. | |
OA18225A (en) | Aminopyrimidinyl compounds as Jak inhibitors. |